The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase1,2. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease3. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity4. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5 , 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD–AD; ref. 7) and dilated cardiomyopathy and conduction-system disease8 (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD–AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

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We thank the PLD patients and their relatives for support and encouragement, and R. Gwilliam for technical support. The following physicians provided clinical details and are responsible for the medical care of many of the patients described: P. Heyburn, R. Temple, R. Greenwood, P. McNally, T. Howlett, R. Corral, A. Johnson, J. Pinkney, J. Reckless and M. Dunnigan. This work had financial support from the British Diabetic Association (Ph.D. Studentship, D.J.L.) and the British Heart Foundation (project grant RCT).

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Author notes

    • Sue Shackleton
    •  & David J. Lloyd

    These authors contributed equally to this work.


  1. Division of Medical Genetics, Departments of Medicine and Genetics, University of Leicester, Leicester, UK .

    • Sue Shackleton
    • , David J. Lloyd
    • , Stephen N.J. Jackson
    •  & Richard C. Trembath
  2. Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Richard Evans
    •  & Simon Gregory
  3. Department of Clinical Genetics, Erasmus University and Academic Hospital Dijkzigt, Rotterdam, The Netherlands .

    • Martinus F. Niermeijer
  4. Diabetes Centre, New Cross Hospital, Wolverhampton , UK.

    • Baldev M. Singh
  5. IV. Med. Klinik m.S. Gastroenterologie, Hepatologie und Endokrinologie, Charite Campus Mitte, Berlin, Germany .

    • Hartmut Schmidt
  6. Abt. Klinische Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany.

    • Georg Brabant
  7. Division of Medical Sciences, Birmingham Heartlands Hospital, University of Birmingham, UK.

    • Sudesh Kumar
  8. University of Manchester, Department of Medicine, Manchester Royal Infirmary, Manchester, UK.

    • Paul N. Durrington
  9. Departments of Medicine and Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

    • Stephen O'Rahilly


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